Atherosclerosis Flashcards
What is atherosclerosis?
A disease of the arteries characterised by a thickening of a portion of the arterial vessel wall closest to the lumen with plaques made up of smooth muscle cells, macrophages and lymphocytes with deposits of cholesterol and other fatty substances
How does atherosclerosis reduce coronary blood flow?
Extra muscle cells and various deposits in the wall bulge out into the lumen of the vessel to increase resistance to flow
Dysfunctional epithelial cells release excess vasoconstrictor and lower than normal amounts of vasodilator
The formation of a coronary thrombosis in the narrow atherosclerotic vessel will trigger…?
MI
Describe how high LDL concentrations can lead to foam cell formation
High concentrations of LDL will migrate into the tunica intima of blood vessels and become oxidised by the action of enzymes such as metalloproteinases released by the dysfunctional endothelium
This promotes the expression of adhesion receptors for leukocytes on the endothelium and t helper cells and monocytes move into the tunica intima. Here monocytes differentiate into macrophages
Macrophages have a scavenger receptor so that it can take up oxidised LDL and this will form a foam cell
How does the formation of foam cells lead to the formation of an atherosclerotic plaque?
Foam cells release chemokines to attract more macrophages to form more foam cells. They also release IGF1 and PDGF which cause smooth muscle proliferation where collagen synthesis is increased so that the plaque hardens
The death of foam cells results in the release of their lipid and DNA content which attracts neutrophils
The foam cells and neutrophils cause local inflammation
T cells which migrate into the tunica intima become activated by macrophages and release many substances including interferon gamma to promote inflammation and attract more leukocytes
This all results in growth of the plaque
What will happen if an atherosclerotic plaque ruptures?
A thrombus will form which will seriously impede blood flow and may lead to MI
The process of atherosclerosis starts with a damaged endothelium. What can cause this damage?
Exposure to LDLs
Exposure to vasoconstrictor hormones associated with hypertension
Exposure to proinflammatory molecules from smoking or excess adipose tissue
Exposure to the products of glycosylation associated with diabetes
What are the risk factors for atherosclerosis?
Increasing age Male Family history of atherosclerosis Hypertension Hyperlipidaemia Diabetes Obesity Smoking
What is a xanthoma?
A sign of hypercholesterolaemia where there are fatty cholesterol rich deposits in the skin usually around the elbows, knees, buttocks and tendons
What is a xanthelasma?
A sign of hypercholesterolaemia where there are fatty deposits around the eyelids
What is arcus senilis?
A sign of hypercholesterolaemia where there is a white ring around the cornea
In familial hypercholesterolaemia what causes the high level of LDL in plasma?
Poor ability to express LDL receptors
What are the secondary causes of hyperlipoproteinaemia?
Diabetes mellitus Alcoholism Hypothyroidism Liver disease Drugs Diet
Describe the exogenous lipid pathway
Fat is digested and absorbed in the small intestine then transported to the blood as a chylomicron where it id then broken down into free fatty acids which are stored in adipose tissue.
This leaves empty HDL and a chylomicron remnant which has an apoE protein on its surface which is recognised by the liver and broken down into fatty acids and cholesterol
Described the endogenous lipid pathway
Free fatty acids and cholesterol in the liver are transported by VLDL to the blood where it is broken down into free fatty acids (which are stored in adipose tissue) leaving LDL which are internalised by the liver to synthesise bile acids or is used by non hepatic tissues for hormone production, cll membrane synthesis or storage
However, if LDL is oxidised then it can be taken up by macrophages to form foam cells
